DESCRPITION: (provided by applicant) The goals of this K24 application are to conduct high quality patient-oriented research and to mentor clinical investigators to career establishment with independent funding. Research accomplishments during the past 4 years: Establishment of a successful, productive research portfolio in the clinical areas of colorectal cancer (CRC) screening, prevention of variceal bleeding, and prognosis of acute upper GI hemorrhage, that has the overarching, unifying theme of understanding and applying risk to tailor management; this includes 23 peer-reviewed publications, 9 papers in review/revision, and several others in preparation; 6 grants recieved, with me as PI on three of them; receipt of awards for research excellence from the American College of Gastroenterology, Foundation of Digestive Health and Nutrition, and IU's Department of Medicine. Mentorship during the past 4 years: 11 mentees have worked with me on the K24 grant during the past 4 years. One each has recieved a K23 grant and a U-01 grant; one has a K23 grant pending; two will complete Masters degrees in Clinical Research (K30HL04150); they have produced 17 manuscripts (8 published, 9 in review/revison ). I teach quantative research methods in 2 new post-graduate courses (Clinical Research Methods, Clinical Trials) and provide mentorship in clinical epidemiology, study design, and quantative and analytic methods. Goals for this application: For research, the goal is to extend the concepts of understanding and applying risk to the clinical areas of screening for CRC, diagnosis of advanced liver disease, treatment to prevent variceal hemorrhage, and management of upper GI hemorrahage with the unifying theme of using patient-specific factors to tailor management. This process involves discerning and understanding the factors that relate to risk; developing and validating a system that simultaneously considers these factors to estimate risk quantitatively; and applying the system to clinical decision-making for individual patients. I have applied this process to these four areas; each is at a different stage of development, with systems of varying degrees of sophistication ( the system for CRC screening is most advanced). During the next cycle, I plan to mature and advanced each system to the point of integration into clinical practice. For mentoring, the goal is to mentor post-graduate fellows and junior faculty to conduct meaningful, high-quality patient oriented research and to guide them to obtain funding through the NIH and VA pathways. For professional growth, the goal is to further develop as a patient-oriented researcher by learning concepts necessary to facilitate the translation of biologic and genetic research from the lab to clinical and patient-oriented settings for the purpose of estimating risk and prognosis. Significance: The fabric of this application is patient-oriented, in that both ongoing and proposed research uses risk to tailor management of specific, prevalent, and burdensome digestive diseases. At an unprecedented time in biological science, there is a great need for experienced researchers, particularly in digestive diseases, to translate findings both from basic research to patient-oriented research and from patient-oriented research to clinical application.